Parasiticidal compounds containing the nsccll3 group



Patented May 22, 1951 PARASITICIDAL COMPOUNDS CONTAINING THE NSCCls GROUP Allen R. Kittleson, Cranford, N. J., assignor to Standard Oil Development Company, a corporation of Delaware No Drawing. Application April 28, 1949;

Serial No. 90,271

20 Claims. (Cl. 16733) This invention relates to new and useful improvements in parasiticidal preparations and more particularly to improved fungicides, insecticides and germicides. This invention also relates to methods of protecting'organic material subject to attack by low orders of organisms. This invention further relates to the synthesis of new chemical compounds, N-thiotrichloromethyl imides of dicarboxylic, acids.

This application is a continuation-in-part of U. S. application No. 773,925, filed September. 13, 1947, now abandoned... I

. It has now been found that a, large number of organic compounds containingv the NSCC13 are'extremely effective for checking the growth of bacteria, fungi, and insects. ,These new compounds may thus be used as novel ingredients of seed and plant protectants because of their disinfecting action on soil containing harmful organisms.

The physiologically active compounds of this invention may thus best be represented as having the NSC'C13 group in which the nitrogen is linked to two carbon atoms, two acyl groups, or one acyl group and. one carbon atom. The phrase acyl group refers to groups of the following character a etc. (see Hackh, Chemical Dictionary, second edition, page 21). When'the nitrogen atom of the NSCCl3 is linked to one acyl group, the compounds may be regarded as amide derivatives; i. e., N-thiotrichloromethyl amides (or N-trichloromethylthio amides). When both of the free linkages of the NSCC13 group are taken up by acyl groups, the compounds may beregarded as N-thiotrichloromethyl imides (or N-trichloromethylthio imides). (See Sidgwicks Organic Chemistry of Nitrogen 1937'edition, pages 136 and 152.)'

Suitable amide compounds of the indicated type are thus illustrated in Formula I:

R-X-NS Cl Formula I in which R represents an organic residue, X is part of an acyl group, such as for example and R. represents an-orgam'c radical or a hydro-- gen radical.

Suitable imide compounds of the indicated type are illustrated by Formula H:

. Formula II in which R represents one or more organic resi:

dues and X ispart of an acyl group, such as for example r The organic residue may be aliphatic, aromatic,

alicyclic, heterocyclic, and their substituted derivatives,

The novel N-thiotrihloromethyl imidecom-i pounds of this invention ,may be preparedv in general by the reaction of perchloromethyl mercaptan (C1SCCl3), With the correspondin imide or the metal salt of this compound. Formula III generally illustrates this reaction where M represents hydrogen or ametal, and where both of. the acyl groups are derived from carboxylic acid where R. is an organic residue. The organic residue may be aliphatic, aromatic, alicyclic, heterocyclic, and their substituted derivatives.

The preparation of the imide starting materials and their metal salts is well known in the art and is not the subject of this invention, and therefore has not been here described.

When the imide salt is used as a starting material for the production of N-thiotrichloromethyl imide derivatives of this invention, the salt is first dispersed in an organic liquid such as benzene or dioxane and while stirring and heating to about 5080 C., an approximately equal molecular quantity of perchloromethyl mercaptan is added over a period of about 1 to 2 hours. The reaction is continued for about 3 to 4 hours after all the mercaptan has been added. After cooling, the reaction mixture is filtered to remove the metal halide and any unreacted imide salt and in some cases, a portion of the N-thiotrichloromethyl imide. The remainder of the N-thiotrichloromethyl imide is recovered by concentrating the solvent filtrate and recrystallizing the residue from a suitable solvent. Any N-thiotrichloromethyl imide in the original filter cake may be recovered by washing with water to remove the metal halide and unreacted imide salt. The water-insoluble product may then be further purified by recrystallization from a suitable solvent.

The compounds of this invention can also be prepared by the general method disclosed in U. S. Serial No. 50,888, filed September 23, 1948, A. R. Kittleson and H. L. Yowell, of dissolving the desired imide, without first forming the metal salt, in aqueous alkaline solution, followed by addition of about an equal molecular quantity of perchloromethyl mercaptan. The mixture is stirred rapidly, conveniently, until the aqueous medium becomes acid to litmus, then filtered and air dried. An 85%-93% yield of N-thitrichloromethyl imide of high purity is thus obtained. The reaction may be carried out at room temperature. In cases where the imide is readily hydrolyzed in alkaline solution, it maybe advantageous to cool the reaction mixture as low as 0 C.

The metal compound used to supply the necessary alkaline solution is a compound of an alkali metal such as lithium, sodium and potassium, and the like. Because of cost factors, sodium and potassium are preferred. The alkali is present preferably in amounts equivalent to the imide used. While other basic compounds may be used, it is desirable to use the alkali hydroxides because of the consequent avoidance of the presence of other anion radicals which might have to be removed.

Variations on these procedures can be made, of course. Thus, the alkali metal imide salts, if available, can be dissolved directly in water and the process further carried on as indicated above for the aqueous solution reaction. The imides can also be dispersed directly in the organic media and finely divided alkali hydroxide or sodium added, thus forming the salt in situ. The process is then further carried on as described above.

The following examples are given to illustrate this invention and include both the preparation of the N-thiotrichloro-methyl imide compounds by both of the indicated methods, the test results obtained on the activity of these organic compounds and others containing the NSCC13 group.

EXAMPLE I N thiotribhloromethyl tetrahydrophthalimide Perchloromethyl mercaptan was reacted with the sodium salt of tetrahydrophthalimide to form N-thiotrichloromethyl tetrahydrophthalimide.

NNa 0180013 O H O stand at'room temperature overnight, afterwhich the precipitated NaCl was filtered ofi. The .filtrate was cooled in an ice bath which resulted in the formation of 40 g. of a white crystalline: precipitate which, on purification by recrystallization from carbon tetrachloride, had .a melting point of l70-172 C. and gave the following analysis:

Per Cent Per Cent PerOent N 01 S Found '4. 38 '34. 40 10. 07 Theory -e 4. 67 35. 50 10.67

EXAMPLE II N -thiotrichloromethyl phthalimide Sixty-eight g. (0.4 mole) of sodium phthalimide was suspended in dry benzene. To this mixture was added a solution of 74.4 g. (0.4 mole) of ClSCCls in cc. of benzene. The reaction mixture was heated to 50-60 C. for four hours, then filtered when hot. The residue (37 g.) consisted of a mixture of sodium chloride and phthalimide. The filtrate was concentrated to half its volume and cooled. This resulted in the.

formation of a while crystalline precipitate (wt.=48 g.) On recrystallization from benzene, the product was essentially odorless and had a melting point of 177 C. Analysis of the product gave the following results:

Per Per Per Per Cent .Gent Cent Cent Found 37.94 1.81 10.16 33.70 Theory for 0 NSCCI; 36.5 1.35 10.81 35.96'

" EXAMPLEIII N-thiotrichloromethyl succim'mide .605 g. of powdered sodium succinimide was an inlet tube for chlorine, a thermometer anda'n outlet tube leading to gas scrubbers containing water.

A slow stream of chlorine was bubbled through Cli s in 00. of benzene in a t 5 the solution at -25 C., cooling being required necked flask equipped with a stirrer, thermomto maintain thi te p t reflux condenser and pp n funnel. .The chlorination was continued until the re- O- the Stirred t e, 93 o 0013 in 0 action mixture had increased 10.5 g. in weight. cc. of benzene was add d slowly from the r p- The solvent was then stripped from theproduct. pin fu During the addition of the ClSCCls 0'. the last quantity being removed at 100 C. under the temperature of the reaction mixture inreduced pressure. creased from C. to C. After all the 71 g. of a straw-colored resinous material was ClSCCls had been added, the reaction mixture recovered which had an odor of sulfur chloride was refluxed for 2 hours at 79-80 C., cooled when warm. to;55,C., and filtered to remove the precipitated 51 The water in the gas scrubbers was titrated NaCl. The filtrate was cooled, giving a white with standard NaOH and found to contain 0.11 crystalline precipitate. g. of product was. remole of HCl indicating that substitution as well covered which, on recrystallization from ethyl as additional chlorination had taken place. alcohol-water mixture, had a melting point of Analysis ofthe final product gave t e fo w 141 C. 2'0 results:

Analysis of the final product gave the following results: Per Cent Per Cent Per Cent Per Per Per it" s? g $233523;0gii6t111333111 23:3 5333 31% Found 5. 51 42.54 12.08 EXAMPLE VI Theory for O N-thiotrz'chloromethyl tetrahydrophthalimz'de H204? A. Four moles (604 g.) of tetrahydrophthalimide, 2500 cc. of water, and 160 g. of sodium hy- /NSCC13 42-92 -9 droxide were charged to a 5-liter flask equipped H: C with a thermometer, stirrer and droppin funnel. After all the imide haddissolved, 744 g. of perchloromethyl mercaptan was added slowly from the dropping funnel. The mercaptan addition EXAMPLE IV required two hours. Rapid agitation was maintained during the addition and for 1/2 hours gggfig'g zz ggg thereafter. The temperature of reaction was 5 maintained at 1015 C. during this entire period. 77.4 g. of ClSCCl3 in 50 cc. of benzene was added The reaction mixture was filtered, washed with toa stirred suspension of sodium endomethylenewater followed by methyl alcohol wash to remove ydrop i 300 0 Of be a small'amount of unreacted perchloromethyl The procedure used in this experiment was the mercaptan. After air drying, 1035 g. (86% yield) e as t a described in Example A total 45 of a white powder was recovered having a melting of 84 g. of white crystalline material was repoint of 171 C. Analysis of the product gave the covered which, on purification by recrystallization following results: from ethyl alcohol, had a melting point of 152-153 C. c Per Per Per Per Per ,Analysis of the final product gave the following 8 3% 3 results:

- Found 34.85 10.67 4.58 36.11 3.12

Per Per Per Theory for Gent Cent Cent /0 N 01 s 55 NSCCla 35.50 10.67 4.57 36.00 2.66 Found 4. 36 33.67 10.40 C/ Theory for I 2 w B. 4,530 g. of tetrahydrophthalimide was dis- He J} persed in 12 liters of. ice and water in a 15 gal. 11, NS 001; 4.49 34.13 10.25 steel drum equipped with two high speed stirrers. H 1240 g. of NaOH dissolved in 12 liters of water I was then added. After solution was complete, I 5,500 g. of perchloromethyl mercaptan was added H over a period of about twelve minutes. The temperature of the reaction mixture at the start was EXAMPLE v 6 C. and was maintained below 14 C. by the addition of ice. Very rapid agitation was main- Chlormated N 'thwmchiorgimethyl tetrahy' tained during the addition of perchloromethyl dmphthamm e mercaptan and for 3 /2 hours thereafter, at which 60 g. (0.2 mole) of thiotrichloromethyl tetrahypoint the reaction mixture became acid to litmus. diophthalimide was dissolved in 150cc. of. car- The mixture was thenfiltered, washedwith water b'on tetrachloride in a 300 cc. flask equipped with followed by a small quantity of methyl alcohol.

1. BLQCQVm'eCi 7,8140? g:-. (87.1%. yield)v of white solid" M. B. 170-17-l C.

EXAMPLE. VII

thermometer.

complete.

and 37.3% chlorine.

Example 1.

reaction mixture stances.

8. intimate contact with. the parasites (see Frear, Chemistry of Insecticides, Fungicides and Herbicides). They may thus be applied as a spray in a liquid carrier, either as asolution in a sol- Pr paration of Nihiotrichloromethyl vent, or as a suspension in a non-solvent; such phthalimide as water. when applied as a spray in water, it

147 g. of phthalimide (practical) and 400 cc. of g ggffigg z g giggi g? alisohol i cParged a zmer flask are soluble in organic solvents such as acetone, equipped w1th a StlIIEl, dropping funnel and 400 cc; of ice and Water contain ethyl alcohol, benzene, naphtha, etc., although ing 40 g. of NaOH were added and the mixture g tg compounds exhlblt dlfierent solubm" stirred until solution of the phthalimide was 1 v Approximately minutes was The water-soluble wetting agents that may bIe' quired for this step. With the temperature of 15 g z g thelsulfi'tes 3 g i 3 2;; r o of 1- SLIC as. O ecano Lip 0C a ecano $11 0113; g gthg l r iigi' ca fgt ain 225s :dded {r051 the droppi amide and ester derivatives, sulfonated aromatic funnel over a period of 5 i u Rapid stirring and mixed alkyl-aryl sulfonate' derivativies, :ster? fatty acids such asthe ricinoleic aci es er 0 was maintained durmg the add1t1on. The temof perature of the reaction mixture increased rapid- $33 5 2 gzg gg g s i f g g i gg g g g ly to 24 C., then slowly decreased. The reaction M solution; became acid to litmus in less than one ik l t z lg loifilde colndegisatioi prl'gdiuczg 8g minute after all of the perchloromethyl mer- 3 ya a enOS y aso euse s I captan had been added. Stirring was continued Pnderstood that these and compouildsaw for an additional five minutes, after which the mtended when the term Wettmg agent 15 used product was filtered, the residue washed with hereafterwater and air dried. Recovered 237 g. of a white h Compounds thls mventlon may also; in powder, the crude product having a melting point admixed with carriers that are themselves active. of 5o 1700 C. Analysis Showed 950% sulfur such as other parasiticldes, hormones, herbicides, fertilizers, and wetting agents. Stomach and contact insecticides such as the arsenates, fluo- EXAMPLE VIII rides, rotenone, and the various fish poisons and Preparation of N-thiQtrichZoro-methyl succinimide organic insecticides, such as di(-p) -chlorophenyl- 9 d 250 t trichloroethane, benzene-hexachloride, and simif ii fi 3 Wa gr lar products may also be advantageously added.

Welv c arge 250 c oi ici wa tzr cz iiizhi riing fo EXANEPLE IX of NaOH was added and the mixture stirred until Compounds of thi invention were tested for solution was comp 186 0f p o yl parasiticidal activity. The compounds tested mercaptan was adde fr h pp f nn l include the new compounds. of this invention over a period of 5 minutes, at which time the 40 as well as other compounds containing the aqueous solution became acid to litmus. The NSCC13 group.

was filtered w th Suctio The values given in column I representv the. washed with water, and ir d Recovered percentage mortality of the test insects after 96 7 3 g. of a white powder having a melting point hours following a two-minute immersion in a of 139-141 C. The melting point of purified 0.25% aqueous solution or suspension of the test N'-thiotrichloromethyl succinimide is 141 C. omp nd,

The compounds described in this invention The results in column II are given as per cent may thus be applied to parent materials to remortality of the test insect after 96 hours foltard or prevent fungus growth and mildew formalowing bloodstream injection of 0.002 cc. of a 5%. tion. Since many of these compounds are exsolution of the test compound. ceptionally nonphytotoxic, they may be applied The slide germination technique for fungicidal safely to a wide variety of plants. Some of the testing was carried out as described by Wellman additional parent materials to which they may and McCallan (Contributions of Boyce Thompbe applied" for protective purposes are leather, son Institute, vol. 3, No. 3, pages 171-176) and is wood, fur, Wool, coated fabrics, and other sublisted in column III as concentration of test compound in per cent to give an LD-50. These compounds may be reduced to an im- It should be noted from the data. below that palpable powder and applied as an undiluted dust the compounds, in addition to being good stomor mixed with a solid carrier, such as clay, talc ach insecticides, were nearly all at least as good and bentonite, as well as other carriers known as, and usually better than, Bordeaux as fungiin the art, in order to bring, the compounds into cides.

Column I Column II Column III Contact Insecticidal Bloodstream In- Fungicidal Inhibiting Con- Actlvlty sect. Activity centration, Per Cent Compound Periplanitus americanc (Amer- Blattella Omelpeltus ican Roach) germam'ca socz'atus Altemeric Sclerotinic (German (Milk Weed 1 solanic fructicola Roach) Bug) Female Male N-thiotrichloromethyl tetrahydrophthalimide 0 5 20 0. 0Dl0. 0001 0. 001-0. 0001 N-thiotrichloromethyl phthalimide 0 5 40 0. 001-0. 0001 Q.00l0. 0 001 N-thiotrl chloromethyl en d o 111 et 11 y 1 en etetrahydrophthal mrde 0 15 20. 0..00l-0..0001. COOL-0.00M. N-tlnotnchloromethylsuccuumide. 15* 40 100 I00 0.UO1.-U.00O1;.

Column III Column I Column II Contact Insecticidal Bloodstream In- Fungicidal Inhibiting Con- Activity sect. Activity centration, Per Cent Compound Per Q americcna (Amer- Blattella Omelpeltus ican Roach) ger Q Alterneria Sclerotinia (German (Milk Weed solrmz'a fructz'cola Roach) Bug) Female Male Chlorinated N,-thiotrichloromethyl tetrahydrophthaliv mifla 5 5 100 100 0. 001 0. 001 N-thiotrichloromethyl 4-nitrophthalim1de" 80 100 0001 0001 N -thiotrichloromethyl 5.5 dlmethyl oxazol1d1ne 2,4 d1one 100 100 100 0001 0001 N-thiotrichloromethyl 5 methyl 5 ethyl oxazolidme 2,4

dione 5 0 100' -100 0001 .0001 N-thiotrichloromethyl 5,5 pentamethylene oxazolidme 1 2,4 dione l0 0 100 80 0001 .0001 N-thiotrichloromethyl 5 phenyl 5 methyl oxazolidme 2,4 dione 0 0 0 80 .001- .0001 .001- .0001 N-thiotrichloromethyl morpholine .01 .001 v .001-7 .0001 N-thigltrlchloromethyl 5-isobutyl 5 methyl oxazohdme 2,4 one N-thiotrichloromethyl 5-cyclopropyl 5 methyl oxazolidine 2,4 dione .1 N-thiotrichloromethyl 2,4 dioxothiazol1dme N-thiotn'chloromethyl o-benzoic sulfimide N -thiotrichloromethyl N -butyl benzene sulfonainide 3-thiotrichloro methyl 5,5 dimethyl hydantom l-nitro 3-thiotrichloromethyl 5,5 dlmethyl hydantoi1 1 l-acetyl 3-thiotrichloromethyl 5,5 djmethyl hydanto1n N-thiotrichloromethyl N-pheuyl benzenesulfonamide... N;thiotrichloromethyl O9 alkanyl succinimide. Bordeaux EXAMPLE X A test on seed disinfecting activity was run.

N thiotrichloromethyl tetrahydrophthalimide In each, ten seeds were planted. The results of Laboratory and field tests have shown that nthiotrichloromethyl tetrahydrophthalimide is effective against the organism causing bacterial spot on the fruit and leaves of peach trees.

Agar-cup-plate studies have shown these compounds to be effective against such organisms as .S'taphylcoccus citreus, Streptococcus hemelytious Streptococcus feccalis and Proteus this experiment are tabulated below r s- Damped Seeds Seedsoff after Condition of Roots when Tr t ng Agent Flamed Germl- Germi-. examined 10 days) Dated nation N n 10 0 N -thiotrichloromethyl tetrahydrophthalimide... 10 5 0 4 healthy rootyst m Commercial Compound "A 10 5 2 None with healthy roots. Commercial Compound "13 10 O The efiectiveness of this compound inthe control of fungi is apparent from the fact'that-seeds treated with a compound of this invention-were the only ones to exhibit healthy root systems.

EXAMPLE In Mildew on Per Cent N -thiotrichloromethyl tetrahydrophthalimide Bean Plants None (control) Very Heavy. 1 N o Complete inhibition of mildew was thus obtained with as little as 0.5% of the indicated compound even though the plant hand been inoculated with mildew spores.

EXAMPLE XII The compounds of this invention also exhibit bactericidal activity.

The n-thiotrichloromethyl imides of this .i'nvention can also be prepared from industrial sources other than the pure chemicalsj I Thus for example it is common practice to frefin'e cracked-gasoline with maleic anhydride to [remove gum forming diolefins. The maleic anhydride diolefin addition product, which normally has little commercial use, 'can' thenbe' converted to mixed imides and then further converted to products of this invention as discussed above. Thus by way of illustration, tetrahydrophthalic anhydride is one of the products obtained from the maleic anhydride refining of cracked gasoline. The tetrahydrophthalic anhydride, on treatment with ammonia, yields the corresponding imide which is then treated with perchloromethyl mercaptan to yield the N-thiotrichloromethyl tetrahydrophthalimide.

It is to be understood that the invention is not limited to the specific examples which have been offered merely as illustrations, since other derivatives can be prepared, and that modifications may be made without departing from the spirit of the invention.

What is claimed is: Y

'1. The method of combatting fungi, bacteria and insects, which comprises distributing a, combination of an organic chemical compound containing the NSCC13 group linked to two carbon atoms of the residual organic compound and a 151- carrier therefor to effect contact of said chemical compound with the fungi, bacteria and insects. 2. In a process for destroying fungi with a fungicidal composition containing an active fungicide wherein the fungicide is distributed by an inert carrier into intimate contact with the fungi, the improvement which comprises employing a chemical compound having the following general formula:

wherein R is .an organic residue.

'6. A parasiticidal composition containing as an active ingredient an organic compound containing the NSCC13 group, linked to two carbon atoms of the residual organic compound, admixed with a surface active dispersing agent which lowers the surface tension of water and thereby promotes aqueous colloidal dispersions of the organic compound.

7. A fungicidal composition comprising an organic compound containing the NSCC13 group linked to two carbon atoms of the residual organic compound dissolved in a solvent therefor.

8. A fungicidal composition comprising an organic compound containing the NSCCl3 group linked to two'carbon'atoms of the residual organic compound admixed with a solid, powdered, inert diluent.

9. A fungicidal com-position comprising as an active ingredient an N-thiotrichlor'omethyl imide of a dicarboxylic acid contained in an aqueous emulsion with a wetting agent.

10. A fungicidal composition comprising as an active ingredient an N-thiotrichloromethyl imide of a dicarboxylic acid dissolved in a solvent therefor.

11. A fungicidal composition comprising as an active ingredient an N-thiotrichloromethyl imide of a dicarboxylic acid, admixed with a surface active dispersing agent which lowers the surface tension of water and thereby promotes aqueous colloidal dispersionsof the imide.

12. The method of combatting fungi, bacteria and insects, which comprises treating material liable'to attack by said funghbacteria and insects, with a composition containing an N-trichloro- :methylthioimide of a dicarboxylic acid as an active ingredient.

13. As a new chemical, N-trichloromethylthio tetrahydrophthalimide.

14. As a new chemical, N-trichloromethylthio phthalimide.

15. As a new chemical, N-trichloromethylthio succini-mide.

16. As a new chemical, N-trichloromethylthio endomethylenetetrahydrophthalimide.

17. As new chemicals, chlorinated N-trichloromethylthio tetrahydrophthalimides.

18. A parasiticidal composition containing an organic compound, N-trichloromethylthio tetrahydrophthalimide, as an active ingredient, admixed with a surface active dispersing agent which lowers the surface tension of water and thereby promotes aqueous colloidal dispersions of the organic compound.

19. A parasit-icidal composition containing an organic compound, N-trichloromethylthio phthalimide, as an active ingredient, admixed with a surface active dispersing agent which lowers the surface tension of water and thereby promotes aqueous colloidal dispersions of the organic compound.

20. A parasiticidal composition containing an organic compound, N-trichloromethylthio succinimide, as an active ingredient, admixed with a surface active dispersing agent which lowers the surface tension of Water and thereby promotes aqueous colloidal dispersions of the organic compound.

ALLEN R. KITTLESON.

No references cited. 

5. AS NEW CHEMICALS, N-THIOTRICHLOROMETHYL IMIDE COMPOUNDS CORRESPONDING TO THE FOLLOWING GENERAL FORMULA: 